Selective organ cooling catheter with guidewire apparatus and temperature-monitoring device

ABSTRACT

A guidable catheter for heating or cooling a surrounding fluid in a feeding vessel in a vasculature of a patient. The catheter includes a heat transfer element, the heat transfer element having a plurality of exterior surface irregularities shaped and arranged to create turbulence in a surrounding fluid. The surface irregularities have a depth at least equal to the boundary layer thickness of flow of the surrounding fluid in the feeding vessel. The catheter assembly also includes a supply catheter having a portion disposed within the heat transfer element to deliver a working fluid to an interior of the heat transfer element. The catheter assembly further includes a return catheter to return a working fluid from the interior of the heat transfer element. A guidewire tube is provided adjacent one of the supply catheter or the return catheter and runs substantially parallel to the axis of the guidable catheter to receive a guidewire disposed within the guidewire tube. The guidable catheter may further have a temperature-monitoring device disposed at the distal tip of the guidewire. The temperature-monitoring device may be a thermocouple or a thermistor. Feedback may further be provided to control the temperature of a source of working fluid. A method is also provided for selectively controlling the temperature of a selected volume of blood in a patient. The method includes introducing a guidewire into a blood vessel feeding a selected volume of blood in a patient and introducing a catheter assembly into the blood vessel feeding a selected volume of blood in a patient by inserting the guidewire into a guidewire tube in the catheter assembly. A working fluid is delivered from a source of working fluid through a supply catheter in the catheter assembly and returned through a return catheter in the catheter assembly. Heat is transferred between a heat transfer element forming a distal end of the catheter assembly and the volume of blood in the feeding vessel. The temperature is monitored of the volume of blood in the feeding vessel by measuring the temperature with a temperature-monitoring device disposed at or near the distal tip of the guidewire.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a continuation-in-part patent application of U.S. patentapplications: Ser. No. 09/103,342, filed on Jun. 23, 1998, and entitled“Selective Organ Cooling Catheter and Method of Using the Same” is nowU.S. Pat. No. 6,096,068; Ser. No. 09/052,545, filed on Mar. 31, 1998,and entitled “Circulating Fluid Hypothermia Method and Apparatus”; Ser.No. 09/047,012, filed on Mar. 24, 1998, and entitled “Improved SelectiveOrgan Hypothermia Method and Apparatus” is now U.S. Pat. No. 5,957,963which is a CIP of Ser. No. 09/012,287 filed Jan. 23, 1998 U.S. Pat. No.6,051,019; Ser. No. 09/215,038, filed on Dec. 16, 1998, and entitled “AnInflatable Catheter for Selective Organ Heating and Cooling and Methodof Using the Same”; Ser. No. 09/215,039, filed on Dec. 16, 1998, andentitled “Method for Low Temperature Thrombolysis and Low TemperatureThrombolytic Agent with Selective Organ Control”; Ser. No. 09/232,177,filed on Jan. 15, 1999, and entitled “Method and Apparatus for Locationand Temperature Specific Drug Action such as Thrombolysis”; and Ser. No.09/246,788, filed on Feb. 9, 1999, and entitled “Triple Lumen Catheterfor Embedding for Method and Device for Applications of Selective OrganCooling”, the entirety of each being incorporated by reference herein.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to the modification and controlof the temperature of a selected body organ. More particularly, theinvention relates to guidewire apparatuses which may be employed tolocate selective organ cooling devices at locations of interest, andguidewire apparatuses which may be further employed to determine thelocal temperature of a volume of blood or tissue in which the guidewireis disposed.

2. Background Information

Organs in the human body, such as the brain, kidney and heart, aremaintained at a constant temperature of approximately 37° C. Hypothermiacan be clinically defined as a core body temperature of 35° C. or less.Hypothermia is sometimes characterized further according to itsseverity. A body core temperature in the range of 33° C. to 35° C. isdescribed as mild hypothermia. A body temperature of 28° C. to 32° C. isdescribed as moderate hypothermia. A body core temperature in the rangeof 24° C. to 28° C. is described as severe hypothermia.

Hypothermia is uniquely effective in reducing brain injury caused by avariety of neurological insults and may eventually play an importantrole in emergency brain resuscitation. Experimental evidence hasdemonstrated that cerebral cooling improves outcome after globalischemia, focal ischemia, or traumatic brain injury. For this reason,hypothermia may be induced in order to reduce the effect of certainbodily injuries to the brain as well as other organs.

Cerebral hypothermia has traditionally been accomplished through wholebody cooling to create a condition of total body hypothermia in therange of 20° C. to 30° C. However, the use of total body hypothermiarisks certain deleterious systematic vascular effects. For example,total body hypothermia may cause severe derangement of thecardiovascular system, including low cardiac output, elevated systematicresistance, and ventricular fibrillation. Other side effects includerenal failure, disseminated intravascular coagulation, and electrolytedisturbances. In addition to the undesirable side effects, total bodyhypothermia is difficult to administer.

Catheters have been developed which are inserted into the bloodstream ofthe patient in order to induce total body hypothermia. For example, U.S.Pat. No. 3,425,419 to Dato describes a method and apparatus of loweringand raising the temperature of the human body. Dato induces moderatehypothermia in a patient using a metallic catheter. The metalliccatheter has an inner passageway through which a fluid, such as water,can be circulated. The catheter is inserted through the femoral vein andthen through the inferior vena cava as far as the right atrium and thesuperior vena cava. The Dato catheter has an elongated cylindrical shapeand is constructed from stainless steel. By way of example, Datosuggests the use of a catheter approximately 70 cm in length andapproximately 6 mm in diameter. However, use of the Dato deviceimplicates the negative effects of total body hypothermia describedabove.

Due to the problems associated with total body hypothermia, attemptshave been made to provide more selective cooling. For example, coolinghelmets or headgear have been used in an attempt to cool only the headrather than the patient's entire body. However, such methods rely onconductive heat transfer through the skull and into the brain. Onedrawback of using conductive heat transfer is that the process ofreducing the temperature of the brain is prolonged. Also, it isdifficult to precisely control the temperature of the brain when usingconduction due to the temperature gradient that must be establishedexternally in order to sufficiently lower the internal temperature. Inaddition, when using conduction to cool the brain, the face of thepatient is also subjected to severe hypothermia, increasing discomfortand the likelihood of negative side effects. It is known that profoundcooling of the face can cause similar cardiovascular side effects astotal body cooling. From a practical standpoint, such devices arecumbersome and may make continued treatment of the patient difficult orimpossible.

Selected organ hypothermia has been accomplished using extracorporealperfusion, as detailed by Arthur E. Schwartz, M. D. et al., in IsolatedCerebral Hypothermia by Single Carotid Artery Perfusion ofExtracorporeally Cooled Blood in Baboons, which appeared in Vol. 39, No.3, NEUROSURGERY 577 (September, 1996). In this study, blood wascontinually withdrawn from baboons through the femoral artery. The bloodwas cooled by a water bath and then infused through a common carotidartery with its external branches occluded. Using this method, normalheart rhythm, systemic arterial blood pressure and arterial blood gasvalues were maintained during the hypothermia. This study showed thatthe brain could be selectively cooled to temperatures of 20° C. withoutreducing the temperature of the entire body. However, externalcirculation of blood is not a practical approach for treating humansbecause the risk of infection, need for anticoagulation, and risk ofbleeding is too great. Further, this method requires cannulation of twovessels making it more cumbersome to perform particularly in emergencysettings. Even more, percutaneous cannulation of the carotid artery isdifficult and potentially fatal due to the associated arterial walltrauma. Finally, this method would be ineffective to cool other organs,such as the kidneys, because the feeding arteries cannot be directlycannulated percutaneously.

Selective organ hypothermia has also been attempted by perfusion of acold solution such as saline or perflourocarbons. This process iscommonly used to protect the heart during heart surgery and is referredto as cardioplegia. Perfusion of a cold solution has a number ofdrawbacks, including a limited time of administration due to excessivevolume accumulation, cost, and inconvenience of maintaining theperfusate and lack of effectiveness due to the temperature dilution fromthe blood. Temperature dilution by the blood is a particular problem inhigh blood flow organs such as the brain.

BRIEF SUMMARY OF THE INVENTION

The invention provides a practical method and apparatus which modifiesand controls the temperature of a selected organ and which may be usedin combination with many complementary therapeutic techniques.

In one aspect, the invention is directed towards a guidable catheter forheating or cooling a surrounding fluid in a feeding vessel in avasculature of a patient. The catheter includes a heat transfer element,the heat transfer element having a plurality of exterior surfaceirregularities shaped and arranged to create turbulence in a surroundingfluid. The surface irregularities have a depth at least equal to theboundary layer thickness of flow of the surrounding fluid in the feedingvessel. The catheter assembly also includes a supply catheter having aportion disposed within the heat transfer element to deliver a workingfluid to an interior of the heat transfer element. The catheter assemblyfurther includes a return catheter to return a working fluid from theinterior of the heat transfer element. A guidewire tube is providedadjacent one of the supply catheter or the return catheter and runssubstantially parallel to the axis of the guidable catheter to receive aguidewire disposed within the guidewire tube.

Implementations of the invention may include one or more of thefollowing. The heat transfer element may have coupled thereto at leastone eyelet configured to receive the guidewire threaded therethrough.The heat transfer element may be formed from at least two heat transfersegments, adjacent heat transfer segments joined by bellows or a thintube, and wherein the eyelets are attached to the heat transfer elementat the bellows or thin tube. In the case of a thin tube, the thin tubemay be formed of a metal or a polymeric material. The surfaceirregularities may include a helical ridge and a helical groove formedon each of successive heat transfer segments; the helical ridge on eachheat transfer segment has an opposite helical twist to the helicalridges on adjacent heat transfer segments. The return catheter may becoaxial with the supply catheter, and the return catheter has a largeror smaller radius than the supply catheter. In another aspect, theinvention is directed towards a guidable catheter for heating or coolinga surrounding fluid in a feeding vessel in a vasculature of a patient,and for determining the temperature of a fluid so heated or cooled. Theguidable catheter has the features described above, and further has atemperature-monitoring device disposed at the distal tip of theguidewire. The temperature-monitoring device may be a thermocouple or athermistor. If a thermistor is used, the same may employ a negativetemperature coefficient of resistance. The thermistor may further have aworking element made of ceramic, and may be encapsulated in glass.

In yet another aspect, the invention is directed toward a deviceincluding a guidable catheter for heating or cooling a surrounding fluidto a predetermined temperature in a feeding vessel in a vasculature of apatient. The device may have the features of the guidable catheterdescribed above and may further include a temperature-monitoring devicedisposed at the distal tip of the guidewire, the temperature monitoringdevice having an output indicative of the sensed temperature. The devicemay further include a temperature-regulated source of working fluidhaving an inlet and an outlet, the supply catheter in pressurecommunication with the inlet and the return catheter in pressurecommunication with the outlet, the source of working fluid having a heatexchange device to change the temperature of the fluid therein uponinput of a signal from the temperature monitoring device.

In a further aspect, the invention is directed towards a method forselectively controlling the temperature of a selected volume of blood ina patient. The method includes introducing a guidewire into a bloodvessel feeding a selected volume of blood in a patient and introducing acatheter assembly into the blood vessel feeding a selected volume ofblood in a patient by inserting the guidewire into a guidewire tube inthe catheter assembly. A working fluid is delivered from a source ofworking fluid through a supply catheter in the catheter assembly andreturned through a return catheter in the catheter assembly. Heat istransferred between a heat transfer element forming a distal end of thecatheter assembly and the volume of blood in the feeding vessel. Thetemperature is monitored of the volume of blood in the feeding vessel bymeasuring the temperature with a temperature-monitoring device disposedat or near the distal tip of the guidewire.

Implementations of the invention may include one or more of thefollowing. The method may further include creating turbulence around aplurality of surface irregularities on the heat transfer element at adistance from the heat transfer element greater than the boundary layerthickness of flow in the feeding vessel, thereby creating turbulencethroughout a free stream of blood flow in the feeding vessel. Thesurface irregularities on the heat transfer element may be a pluralityof segments of helical ridges and grooves having alternating directionsof helical rotation. In this case, turbulence is created by establishingrepetitively alternating directions of helical blood flow with thealternating helical rotations of the ridges and grooves. The guidewiremay be inserted through at least one eyelet on the heat transferelement. The method may further include feeding back a signal indicativeof the monitored temperature from the temperature monitoring device tothe source of working fluid to alter the temperature of the workingfluid.

Advantages of the invention include the following. The inventionprovides a highly efficient device and method for cooling or heatingblood or other bodily fluids, and further provides a device and methodto measure the temperature of the blood or other bodily fluids whosetemperature has been so modified. A signal indicative of the temperaturemeasured may be fed back into a control circuit coupled to a source ofworking fluid to provide an even more accurate control of temperature.The invention further provides a method and device to guide a catheterwith a heat transfer element through tortuous vasculature.

The novel features of this invention, as well as the invention itself,will be best understood from the attached drawings, taken along with thefollowing description, in which similar reference characters refer tosimilar parts, and in which:

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 is a front view of a first embodiment of a turbulence inducingheat transfer element according to the principles of the inventionwithin an artery;

FIG. 2 is a more detailed front view of the heat transfer element ofFIG. 1;

FIG. 3 is a front sectional view of the heat transfer element of FIG. 1;

FIG. 4 is a transverse sectional view of the heat transfer element ofFIG. 1;

FIG. 5 is a front perspective view of the heat transfer element of FIG.1 in use within a partially broken away blood vessel;

FIG. 6 is a partially broken away front perspective view of a secondembodiment of a turbulence inducing heat transfer element according tothe principles of the invention;

FIG. 7 is a transverse sectional view of the heat transfer element ofFIG. 6;

FIG. 8 is a schematic representation of the invention being used to coolthe brain of a patient;

FIG. 9 is a front sectional view of a guide catheter according to anembodiment of the invention which may be employed for applications ofthe heat transfer element according to the principles of the invention;

FIG. 10 is a front sectional view of a third embodiment of a catheteremploying a heat transfer element according to the principles of theinvention further employing a return tube/guide catheter;

FIG. 11 is a front sectional view of a fourth embodiment of a catheteremploying a heat transfer element according to the principles of theinvention further employing a delivery catheter;

FIG. 12 is a front sectional view of the fourth embodiment of FIG. 11further employing a working fluid catheter;

FIG. 13 is a front sectional view of a fifth embodiment of a catheteremploying a heat transfer element according to the principles of theinvention further employing a guidewire;

FIG. 14 is a front sectional view of a sixth embodiment of a catheteremploying a heat transfer element according to the principles of theinvention further employing a delivery/working fluid catheter with aballoon attachment;

FIG. 15 is a second front sectional view of the sixth embodiment of FIG.14 shown with the balloon attachment occluding an opening in the heattransfer element;

FIG. 16 is a front sectional view of a seventh embodiment of a catheteremploying a heat transfer element according to the principles of theinvention further employing a delivery lumen;

FIG. 17 is a front sectional view of an eighth embodiment of a catheteremploying a heat transfer element according to the principles of theinvention further employing a delivery lumen, this delivery lumennon-coaxial with the central body of the catheter;

FIG. 18 is a front sectional view of a ninth embodiment of a catheteremploying a heat transfer element according to the principles of theinvention further employing a delivery lumen, this delivery lumennon-coaxial with the central body of the catheter;

FIG. 19 is a front sectional view of a tenth embodiment of a catheteremploying a heat transfer element according to the principles of theinvention further employing multiple lumens;

FIG. 20 is a cross-sectional view of the tenth embodiment of FIG. 19,taken along lines 20—20 of FIG. 19;

FIG. 21 is a front sectional view of an eleventh embodiment of acatheter employing a heat transfer element according to the principlesof the invention;

FIG. 22 is a side sectional view of a further embodiment of theinvention featuring an embodiment of a guidewire apparatus which may beemployed to maneuver the catheter into a predetermined position;

FIG. 23 is a side section view of a further embodiment of the inventionfeaturing an embodiment of a temperature monitoring device, in the formof a thermocouple, which may be employed to determine the localtemperature of a volume of blood or tissue in which the guidewire islocated; and

FIG. 24 is a side section view of a further embodiment of the inventionfeaturing an embodiment of a temperature monitoring device, in the formof a thermistor, which may be employed to determine the localtemperature of a volume of blood or tissue in which the guidewire islocated.

FIG. 25 is a schematic diagram of an embodiment of the invention showinga feedback loop to a temperature-controlled source of working fluid.

DETAILED DESCRIPTION OF THE INVENTION

The temperature of a selected organ may be intravascularly regulated bya heat transfer element placed in the organ's feeding artery to absorbor deliver heat to or from the blood flowing into the organ. While themethod is described with respect to blood flow into an organ, it isunderstood that heat transfer within a volume of tissue is analogous. Inthe latter case, heat transfer is predominantly by conduction.

The heat transfer may cause either a cooling or a heating of theselected organ. A heat transfer element that selectively alters thetemperature of an organ should be capable of providing the necessaryheat transfer rate to produce the desired cooling or heating effectwithin the organ to achieve a desired temperature.

The heat transfer element should be small and flexible enough to fitwithin the feeding artery while still allowing a sufficient blood flowto reach the organ in order to avoid ischemic organ damage. Feedingarteries, like the carotid artery, branch off the aorta at variouslevels. Subsidiary arteries continue to branch off these initialbranches. For example, the internal carotid artery branches off thecommon carotid artery near the angle of the jaw. The heat transferelement is typically inserted into a peripheral artery, such as thefemoral artery, using a guide catheter or guidewire (see below), andaccesses a feeding artery by initially passing though a series of one ormore of these branches. Thus, the flexibility and size, e.g., thediameter, of the heat transfer element are important characteristics.This flexibility is achieved as is described in more detail below.

These points are illustrated using brain cooling as an example. Thecommon carotid artery supplies blood to the head and brain. The internalcarotid artery branches off the common carotid artery to supply blood tothe anterior cerebrum. The heat transfer element may be placed into thecommon carotid artery or into both the common carotid artery and theinternal carotid artery.

The benefits of hypothermia described above are achieved when thetemperature of the blood flowing to the brain is reduced to between 30°C. and 32° C. A typical brain has a blood flow rate through each carotidartery (right and left) of approximately 250-375 cubic centimeters perminute (cc/min). With this flow rate, calculations show that the heattransfer element should absorb approximately 75-175 watts of heat whenplaced in one of the carotid arteries to induce the desired coolingeffect. Smaller organs may have less blood flow in their respectivesupply arteries and may require less heat transfer, such as about 25watts.

The method employs conductive and convective heat transfers. Once thematerials for the device and a working fluid are chosen, the conductiveheat transfers are solely dependent on the temperature gradients.Convective heat transfers, by contrast, also rely on the movement offluid to transfer heat. Forced convection results when the heat transfersurface is in contact with a fluid whose motion is induced (or forced)by a pressure gradient, area variation, or other such force. In the caseof arterial flow, the beating heart provides an oscillatory pressuregradient to force the motion of the blood in contact with the heattransfer surface. One of the aspects of the device uses turbulence toenhance this forced convective heat transfer.

The rate of convective heat transfer Q is proportional to the product ofS, the area of the heat transfer element in direct contact with thefluid, ΔT=T_(b)−T_(s), the temperature differential between the surfacetemperature T_(s) of the heat transfer element and the free stream bloodtemperature T_(b), and {overscore (h_(c)+L )}, the average convectionheat transfer coefficient over the heat transfer area. {overscore(h_(c)+L )} is sometimes called the “surface coefficient of heattransfer” or the “convection heat transfer coefficient”.

The magnitude of the heat transfer rate Q to or from the fluid flow canbe increased through manipulation of the above three parameters.Practical constraints limit the value of these parameters and how muchthey can be manipulated. For example, the internal diameter of thecommon carotid artery ranges from 6 to 8 mm. Thus, the heat transferelement residing therein may not be much larger than 4 mm in diameter toavoid occluding the vessel. The length of the heat transfer elementshould also be limited. For placement within the internal and commoncarotid artery, the length of the heat transfer element is limited toabout 10 cm. This estimate is based on the length of the common carotidartery, which ranges from 8 to 12 cm.

Consequently, the value of the surface area S is limited by the physicalconstraints imposed by the size of the artery into which the device isplaced. Surface features, such as fins, can be used to increase thesurface area of the heat transfer element, however, these features alonecannot provide enough surface area enhancement to meet the required heattransfer rate to effectively cool the brain.

One may also attempt to vary the magnitude of the heat transfer rate byvarying ΔT. The value of ΔT=T_(b)−T_(s) can be varied by varying thesurface temperature T_(s) of the heat transfer element. The allowablesurface temperature of the heat transfer element is limited by thecharacteristics of blood. The blood temperature is fixed at about 37°C., and blood freezes at approximately 0° C. When the blood approachesfreezing, ice emboli may form in the blood which may lodge downstream,causing serious ischemic injury. Furthermore, reducing the temperatureof the blood also increases its viscosity which results in a smalldecrease in the value of {overscore (h_(c)+L )}. Increased viscosity ofthe blood may further result in an increase in the pressure drop withinthe artery, thus compromising the flow of blood to the brain. Given theabove constraints, it is advantageous to limit the surface temperatureof the heat transfer element to approximately 1° C.-5° C., thusresulting in a maximum temperature differential between the blood streamand the heat transfer element of approximately 32° C.-36° C.

One may also attempt to vary the magnitude of the heat transfer rate byvarying {overscore (h_(c)+L )}. Fewer constraints are imposed on thevalue of the convection heat transfer coefficient {overscore (h_(c)+L)}. The mechanisms by which the value of {overscore (h_(c)+L )} may beincreased are complex. However, one way to increase {overscore (h_(c)+L)} for a fixed mean value of the velocity is to increase the level ofturbulent kinetic energy in the fluid flow.

The heat transfer rate Q_(no-flow) in the absence of fluid flow isproportional to ΔT, the temperature differential between the surfacetemperature T_(s) of the heat transfer element and the free stream bloodtemperature T_(b) times k, the diffusion constant, and is inverselyproportion to δ, the thickness of the boundary layer.

The magnitude of the enhancement in heat transfer by fluid flow can beestimated by taking the ratio of the heat transfer rate with fluid flowto the heat transfer rate in the absence of fluid flowN=Q_(flow)/Q_(no-flow)={overscore (h_(c)+L )}/(k/δ). This ratio iscalled the Nusselt number (“Nu”). For convective heat transfer betweenblood and the surface of the heat transfer element, Nusselt numbers of30-80 have been found to be appropriate for selective coolingapplications of various organs in the human body. Nusselt numbers aregenerally dependent on several other numbers: the Reynolds number, theWomersley number, and the Prandtl number.

Stirring-type mechanisms, which abruptly change the direction ofvelocity vectors, may be utilized to induce turbulent kinetic energy andincrease the heat transfer rate. The level of turbulence so created ischaracterized by the turbulence intensity . Turbulence intensity isdefined as the root mean square of the fluctuating velocity divided bythe mean velocity. Such mechanisms can create high levels of turbulenceintensity in the free stream, thereby increasing the heat transfer rate.This turbulence intensity should ideally be sustained for a significantportion of the cardiac cycle, and should ideally be created throughoutthe free stream and not just in the boundary layer.

Turbulence does occur for a short period in the cardiac cycle anyway. Inparticular, the blood flow is turbulent during a small portion of thedescending systolic flow. This portion is less than 20% of the period ofthe cardiac cycle. If a heat transfer element is placed co-axiallyinside the artery, the heat transfer rate will be enhanced during thisshort interval. For typical of these fluctuations, the turbulenceintensity is at least 0.05. In other words, the instantaneous velocityfluctuations deviate from the mean velocity by at least 5%. Althoughideally turbulence is created throughout the entire period of thecardiac cycle, the benefits of turbulence are obtained if the turbulenceis sustained for 75%, 50% or even as low as 30% or 20% of the cardiaccycle.

One type of turbulence-inducing heat transfer element which may beadvantageously employed to provide heating or cooling of an organ orvolume is described in co-pending U.S. patent application Ser. No.09/103,342 to Dobak and Lasheras for a “Selective Organ Cooling Catheterand Method of Using the Same,” incorporated by reference above. In thatapplication, and as described below, the heat transfer element is madeof a high thermal conductivity material, such as metal. The use of ahigh thermal conductivity material increases the heat transfer rate fora given temperature differential between the coolant within the heattransfer element and the blood. This facilitates the use of a highertemperature coolant within the heat transfer element, allowing safercoolants, such as water, to be used. Highly thermally conductivematerials, such as metals, tend to be rigid. In that application,bellows provided a high degree of articulation that compensated for theintrinsic stiffness of the metal. In another application incorporated byreference above, the bellows are replaced with a straight metal tubehaving a predetermined thickness to allow flexibility via bending of themetal. Alternatively, the bellows may be replaced with a polymer tube,e.g., a latex rubber tube, a plastic tube, or a flexible plasticcorrugated tube.

The device size may be minimized, e.g., less than 4 mm, to preventblockage of the blood flowing in the artery. The design of the heattransfer element should facilitate flexibility in an inherentlyinflexible material.

To create the desired level of turbulence intensity in the blood freestream during the whole cardiac cycle, one embodiment of the device usesa modular design. This design creates helical blood flow and produces ahigh level of turbulence in the free stream by periodically forcingabrupt changes in the direction of the helical blood flow. FIG. 1 is aperspective view of such a turbulence inducing heat transfer elementwithin an artery. Turbulent flow would be found at point 114, in thefree stream area. The abrupt changes in flow direction are achievedthrough the use of a series of two or more heat transfer segments, eachcomprised of one or more helical ridges. To affect the free stream, thedepth of the helical ridge is larger than the thickness of the boundarylayer which would develop if the heat transfer element had a smoothcylindrical surface.

The use of periodic abrupt changes in the helical direction of the bloodflow in order to induce strong free stream turbulence may be illustratedwith reference to a common clothes washing machine. The rotor of awashing machine spins initially in one direction causing laminar flow.When the rotor abruptly reverses direction, significant turbulentkinetic energy is created within the entire wash basin as the changingcurrents cause random turbulent motion within the clothes-water slury.

In the following description, the term “pressure communication” is usedto describe a situation between two points in a flow or in a standingfluid. If pressure is applied at one point, the second point willeventually feel effects of the pressure if the two points are inpressure communication. Any number of valves or elements may be disposedbetween the two points, and the two points may still be in pressurecommunication if the above test is met. For example, for a standingfluid in a pipe, any number of pipe fittings may be disposed between twopipes and, so long as an open path is maintained, points in therespective pipes may still be in pressure communication.

FIG. 2 is an elevation view of one embodiment of a heat transfer element14. The heat transfer element 14 is comprised of a series of elongated,articulated segments or modules 20, 22, 24. Three such segments areshown in this embodiment, but two or more such segments could be used.As seen in FIG. 2, a first elongated heat transfer segment 20 is locatedat the proximal end of the heat transfer element 14. Aturbulence-inducing exterior surface of the segment 20 comprises fourparallel helical ridges 28 with four parallel helical grooves 26therebetween. One, two, three, or more parallel helical ridges 28 couldalso be used. In this embodiment, the helical ridges 28 and the helicalgrooves 26 of the heat transfer segment 20 have a left hand twist,referred to herein as a counter-clockwise spiral or helical rotation, asthey proceed toward the distal end of the heat transfer segment 20.

The first heat transfer segment 20 is coupled to a second elongated heattransfer segment 22 by a first tube section 25, which providesflexibility. The second heat transfer segment 22 comprises one or morehelical ridges 32 with one or more helical grooves 30 therebetween. Theridges 32 and grooves 30 have a right hand, or clockwise, twist as theyproceed toward the distal end of the heat transfer segment 22. Thesecond heat transfer segment 22 is coupled to a third elongated heattransfer segment 24 by a second tube section 27. The third heat transfersegment 24 comprises one or more helical ridges 36 with one or morehelical grooves 34 therebetween. The helical ridge 36 and the helicalgroove 34 have a left hand, or counter-clockwise, twist as they proceedtoward the distal end of the heat transfer segment 24. Thus, successiveheat transfer segments 20, 22, 24 of the heat transfer element 14alternate between having clockwise and counterclockwise helical twists.The actual left or right hand twist of any particular segment isimmaterial, as long as adjacent segments have opposite helical twist.

In addition, the rounded contours of the ridges 28, 32, 36 also allowthe heat transfer element 14 to maintain a relatively atraumaticprofile, thereby minimizing the possibility of damage to the bloodvessel wall. A heat transfer element may be comprised of two, three, ormore heat transfer segments.

The tube sections 25, 27 are formed from seamless and nonporousmaterials, such as metal, and therefore are impermeable to gas, whichcan be particularly important, depending on the type of working fluidthat is cycled through the heat transfer element 14. The structure ofthe tube sections 25, 27 allows them to bend, extend and compress, whichincreases the flexibility of the heat transfer element 14 so that it ismore readily able to navigate through blood vessels. The tube sections25, 27 are also able to tolerate cryogenic temperatures without a lossof performance. The tube sections 25, 27 may have a predeterminedthickness of their walls, such as between about 0.5 and 0.8 mils. Thepredetermined thickness is to a certain extent dependent on the diameterof the overall tube. Thicknesses of 0.5 to 0.8 mils may be appropriateespecially for a tubal diameter of about 4 mm. For smaller diameters,such as about 3.3 mm, larger thicknesses may be employed for higherstrength. In another embodiment, tube sections 25, 27 may be formed froma polymer material such as rubber, e.g., latex rubber.

The exterior surfaces of the heat transfer element 14 can be made frommetal except in flexible joint embodiments where the surface may becomprised of a polymer material. The metal may be a very high thermalconductivity material such as nickel, thereby facilitating efficientheat transfer. Alternatively, other metals such as stainless steel,titanium, aluminum, silver, copper and the like, can be used, with orwithout an appropriate coating or treatment to enhance biocompatibilityor inhibit clot formation. Suitable biocompatible coatings include,e.g., gold, platinum or polymer paralyene. The heat transfer element 14may be manufactured by plating a thin layer of metal on a mandrel thathas the appropriate pattern. In this way, the heat transfer element 14may be manufactured inexpensively in large quantities, which is animportant feature in a disposable medical device.

Because the heat transfer element 14 may dwell within the blood vesselfor extended periods of time, such as 24-48 hours or even longer, it maybe desirable to treat the surfaces of the heat transfer element 14 toavoid clot formation. One means by which to prevent thrombus formationis to bind an antithrombogenic agent to the surface of the heat transferelement 14. For example, heparin is known to inhibit clot formation andis also known to be useful as a biocoating. Alternatively, the surfacesof the heat transfer element 14 may be bombarded with ions such asnitrogen. Bombardment with nitrogen can harden and smooth the surfaceand, thus prevent adherence of clotting factors to the surface.

FIG. 3 is a longitudinal sectional view of the heat transfer element 14,taken along line 3-3 in FIG. 2. Some interior contours are omitted forpurposes of clarity. An inner tube 42 creates an inner coaxial lumen 40and an outer coaxial lumen 46 within the heat transfer element 14. Oncethe heat transfer element 14 is in place in the blood vessel, a workingfluid such as saline or other aqueous solution may be circulated throughthe heat transfer element 14. Fluid flows up a supply catheter into theinner coaxial lumen 40. At the distal end of the heat transfer element14, the working fluid exits the inner coaxial lumen 40 and enters theouter lumen 46. As the working fluid flows through the outer lumen 46,heat is transferred between the working fluid and the exterior surface37 of the heat transfer element 14. Because the heat transfer element 14is constructed from a high conductivity material, the temperature of itsexterior surface 37 may reach very close to the temperature of theworking fluid. The tube 42 may be formed as an insulating divider tothermally separate the inner lumen 40 from the outer lumen 46. Forexample, insulation may be achieved by creating longitudinal airchannels in the wall of the insulating tube 42. Alternatively, theinsulating tube 42 may be constructed of a non-thermally conductivematerial like polytetrafluoroethylene or some other polymer.

It is important to note that the same mechanisms that govern the heattransfer rate between the exterior surface 37 of the heat transferelement 14 and the blood also govern the heat transfer rate between theworking fluid and the interior surface 38 of the heat transfer element14. The heat transfer characteristics of the interior surface 38 areparticularly important when using water, saline or other fluid whichremains a liquid as the coolant. Other coolants such as freon undergonucleate boiling and create turbulence through a different mechanism.Saline is a safe coolant because it is non-toxic, and leakage of salinedoes not result in a gas embolism, which could occur with the use ofboiling refrigerants. Since turbulence in the coolant is enhanced by theshape of the interior surface 38 of the heat transfer element 14, thecoolant can be delivered to the heat transfer element 14 at a warmertemperature and still achieve the necessary heat transfer rate.

This has a number of beneficial implications in the need for insulationalong the catheter shaft length. Due to the decreased need forinsulation, the catheter shaft diameter can be made smaller. Theenhanced heat transfer characteristics of the interior surface of theheat transfer element 14 also allow the working fluid to be delivered tothe heat transfer element 14 at lower flow rates and lower pressures.High pressures may make the heat transfer element stiff and cause it topush against the wall of the blood vessel, thereby shielding part of theexterior surface 37 of the heat transfer element 14 from the blood.Because of the increased heat transfer characteristics achieved by thealternating helical ridges 28, 32, 36, the pressure of the working fluidmay be as low as 5 atmospheres, 3 atmospheres, 2 atmospheres or evenless than 1 atmosphere.

FIG. 4 is a transverse sectional view of the heat transfer element 14,taken at a location denoted by the line 4—4 in FIG. 2. FIG. 4illustrates a five-lobed embodiment, whereas FIG. 2 illustrates afour-lobed embodiment. As mentioned earlier, any number of lobes mightbe used. In FIG. 4, the coaxial construction of the heat transferelement 14 is clearly shown. The inner coaxial lumen 40 is defined bythe insulating coaxial tube 42. The outer lumen 46 is defined by theexterior surface of the insulating coaxial tube 42 and the interiorsurface 38 of the heat transfer element 14. In addition, the helicalridges 32 and helical grooves 30 may be seen in FIG. 4. As noted above,in the preferred embodiment, the depth of the grooves, d_(i), is greaterthan the boundary layer thickness which would have developed if acylindrical heat transfer element were introduced. For example, in aheat transfer element 14 with a 4 mm outer diameter, the depth of theinvaginations, d_(i), may be approximately equal to 1 mm if designed foruse in the carotid artery. Although FIG. 4 shows four ridges and fourgrooves, the number of ridges and grooves may vary. Thus, heat transferelements with 1, 2, 3, 4, 5, 6, 7, 8 or more ridges are specificallycontemplated.

FIG. 5 is a perspective view of a heat transfer element 14 in use withina blood vessel, showing only one helical lobe per segment for purposesof clarity. Beginning from the proximal end of the heat transfer element(not shown in FIG. 5), as the blood moves forward during the systolicpulse, the first helical heat transfer segment 20 induces acounter-clockwise rotational inertia to the blood. As the blood reachesthe second segment 22, the rotational direction of the inertia isreversed, causing turbulence within the blood. Further, as the bloodreaches the third segment 24, the rotational direction of the inertia isagain reversed. The sudden changes in flow direction actively reorientand randomize the velocity vectors, thus ensuring turbulence throughoutthe bloodstream. During turbulent flow, the velocity vectors of theblood become more random and, in some cases, become perpendicular to theaxis of the artery. In addition, as the velocity of the blood within theartery decreases and reverses direction during the cardiac cycle,additional turbulence is induced and turbulent motion is sustainedthroughout the duration of each pulse through the same mechanismsdescribed above.

Thus, a large portion of the volume of warm blood in the vessel isactively brought in contact with the heat transfer element 14, where itcan be cooled by direct contact rather than being cooled largely byconduction through adjacent laminar layers of blood. As noted above, thedepth of the grooves 26, 30, 34 (FIG. 2) is greater than the depth ofthe boundary layer that would develop if a straight-walled heat transferelement were introduced into the blood stream. In this way, free streamturbulence is induced. In the preferred embodiment, in order to createthe desired level of turbulence in the entire blood stream during thewhole cardiac cycle, the heat transfer element 14 creates a turbulenceintensity greater than about 0.05. The turbulence intensity may begreater than 0.05, 0.06, 0.07 or up to 0.10 or 0.20 or greater.

Referring back to FIG. 2, the heat transfer element 14 has been designedto address all of the design criteria discussed above. First, the heattransfer element 14 is flexible and is made of a highly conductivematerial. The flexibility is provided by a segmental distribution oftube sections 25, 27 which provide an articulating mechanism. The tubesections have a predetermined thickness which provides sufficientflexibility. Second, the exterior surface area 37 has been increasedthrough the use of helical ridges 28, 32, 36 and helical grooves 26, 30,34. The ridges also allow the heat transfer element 14 to maintain arelatively atraumatic profile, thereby minimizing the possibility ofdamage to the vessel wall. Third, the heat transfer element 14 has beendesigned to promote turbulent kinetic energy both internally andexternally. The modular or segmental design allows the direction of theinvaginations to be reversed between segments. The alternating helicalrotations create an alternating flow that results in a mixing of theblood in a manner analogous to the mixing action created by the rotor ofa washing machine that switches directions back and forth. This mixingaction is intended to promote high level turbulent kinetic energy toenhance the heat transfer rate. The alternating helical design alsocauses beneficial mixing, or turbulent kinetic energy, of the workingfluid flowing internally.

FIG. 6 is a cut-away perspective view of an alternative embodiment of aheat transfer element 50. An external surface 52 of the heat transferelement 50 is covered with a series of axially staggered protrusions 54.The staggered nature of the outer protrusions 54 is readily seen withreference to FIG. 7 which is a transverse cross-sectional view taken ata location denoted by the line 7—7 in FIG. 6. In order to induce freestream turbulence, the height, d_(p), of the staggered outer protrusions54 is greater than the thickness of the boundary layer which woulddevelop if a smooth heat transfer element had been introduced into theblood stream. As the blood flows along the external surface 52, itcollides with one of the staggered protrusions 54 and a turbulent wakeflow is created behind the protrusion. As the blood divides and swirlsalong side of the first staggered protrusion 54, its turbulent wakeencounters another staggered protrusion 54 within its path preventingthe re-lamination of the flow and creating yet more turbulence. In thisway, the velocity vectors are randomized and turbulence is created notonly in the boundary layer but also throughout the free stream. As isthe case with the preferred embodiment, this geometry also induces aturbulent effect on the internal coolant flow.

A working fluid is circulated up through an inner coaxial lumen 56defined by an insulating coaxial tube 58 to a distal tip of the heattransfer element 50. The working fluid then traverses an outer coaxiallumen 60 in order to transfer heat to the exterior surface 52 of theheat transfer element 50. The inside surface of the heat transferelement 50 is similar to the exterior surface 52, in order to induceturbulent flow of the working fluid. The inner protrusions can bealigned with the outer protrusions 54, as shown in FIG. 7, or they canbe offset from the outer protrusions 54, as shown in FIG. 6.

FIG. 8 is a schematic representation of the invention being used to coolthe brain of a patient. The selective organ hypothermia apparatus shownin FIG. 8 includes a working fluid supply 10, preferably supplying achilled liquid such as water, alcohol or a halogenated hydrocarbon, asupply catheter 12 and the heat transfer element 14. The supply catheter12 has a coaxial construction. An inner coaxial lumen within the supplycatheter 12 receives coolant from the working fluid supply 10. Thecoolant travels the length of the supply catheter 12 to the heattransfer element 14 which serves as the cooling tip of the catheter. Atthe distal end of the heat transfer element 14, the coolant exits theinsulated interior lumen and traverses the length of the heat transferelement 14 in order to decrease the temperature of the heat transferelement 14. The coolant then traverses an outer lumen of the supplycatheter 12 so that it may be disposed of or recirculated. The supplycatheter 12 is a flexible catheter having a diameter sufficiently smallto allow its distal end to be inserted percutaneously into an accessibleartery such as the femoral artery of a patient as shown in FIG. 8. Thesupply catheter 12 is sufficiently long to allow the heat transferelement 14 at the distal end of the supply catheter 12 to be passedthrough the vascular system of the patient and placed in the internalcarotid artery or other small artery. The method of inserting thecatheter into the patient and routing the heat transfer element 14 intoa selected artery is well known in the art.

Although the working fluid supply 10 is shown as an exemplary coolingdevice, other devices and working fluids may be used. For example, inorder to provide cooling, freon, perflourocarbon, water, or saline maybe used, as well as other such coolants.

The heat transfer element can absorb or provide over 75 Watts of heat tothe blood stream and may absorb or provide as much as 100 Watts, 150Watts, 170 Watts or more. For example, a heat transfer element with adiameter of 4 mm and a length of approximately 10 cm using ordinarysaline solution chilled so that the surface temperature of the heattransfer element is approximately 5° C. and pressurized at 2 atmospherescan absorb about 100 Watts of energy from the bloodstream. Smallergeometry heat transfer elements may be developed for use with smallerorgans which provide 60 Watts, 50 Watts, 25 Watts or less of heattransfer.

The practice of the present invention is illustrated in the followingnon-limiting example.

Exemplary Procedure

1. The patient is initially assessed, resuscitated, and stabilized.

2. The procedure is carried out in an angiography suite or surgicalsuite equipped with fluoroscopy.

3. Because the catheter is placed into the common carotid artery, it isimportant to determine the presence of stenotic atheromatous lesions. Acarotid duplex (Doppler/ultrasound) scan can quickly and non-invasivelymake this determination. The ideal location for placement of thecatheter is in the left carotid so this may be scanned first. If diseaseis present, then the right carotid artery can be assessed. This test canbe used to detect the presence of proximal common carotid lesions byobserving the slope of the systolic upstroke and the shape of thepulsation. Although these lesions are rare, they could inhibit theplacement of the catheter. Examination of the peak blood flow velocitiesin the internal carotid can determine the presence of internal carotidartery lesions. Although the catheter is placed proximally to suchlesions, the catheter may exacerbate the compromised blood flow createdby these lesions. Peak systolic velocities greater that 130 cm/sec andpeak diastolic velocities>100 cm/sec in the internal indicate thepresence of at least 70% stenosis. Stenosis of 70% or more may warrantthe placement of a stent to open up the internal artery diameter.

4. The ultrasound can also be used to determine the vessel diameter andthe blood flow and the catheter with the appropriately sized heattransfer element could be selected.

5. After assessment of the arteries, the patients inguinal region issterilely prepped and infiltrated with lidocaine.

6. The femoral artery is cannulated and a guidewire may be inserted tothe desired carotid artery. Placement of the guidewire is confirmed withfluoroscopy.

7. An angiographic catheter can be fed over the wire and contrast mediainjected into the artery to further to assess the anatomy of thecarotid.

8. Alternatively, the femoral artery is cannulated and a 10-12.5 french(f) introducer sheath is placed.

9. A guide catheter is placed into the desired common carotid artery. Ifa guiding catheter is placed, it can be used to deliver contrast mediadirectly to further assess carotid anatomy.

10. A 10 f-12 f (3.3-4.0 mm) (approximate) cooling catheter issubsequently filled with saline and all air bubbles are removed.

11. The cooling catheter is placed into the carotid artery via theguiding catheter or over the guidewire. Placement is confirmed withfluoroscopy.

12. Alternatively, the cooling catheter tip is shaped (angled or curvedapproximately 45 degrees), and the cooling catheter shaft has sufficientpushability and torqueability to be placed in the carotid without theaid of a guidewire or guide catheter.

13. The cooling catheter is connected to a pump circuit also filled withsaline and free from air bubbles. The pump circuit has a heat exchangesection that is immersed into a water bath and tubing that is connectedto a peristaltic pump. The water bath is chilled to approximately 0° C.

14. Cooling is initiated by starting the pump mechanism. The salinewithin the cooling catheter is circulated at 5 cc/sec. The salinetravels through the heat exchanger in the chilled water bath and iscooled to approximately 1° C.

15. The saline subsequently enters the cooling catheter where it isdelivered to the heat transfer element. The saline is warmed toapproximately 5-7° C. as it travels along the inner lumen of thecatheter shaft to the end of the heat transfer element.

16. The saline then flows back through the heat transfer element incontact with the inner metallic surface. The saline is further warmed inthe heat transfer element to 12-15° C., and in the process, heat isabsorbed from the blood, cooling the blood to 30° C. to 32° C.

17. The chilled blood then goes on to chill the brain. It is estimatedthat 15-30 minutes will be required to cool the brain to 30 to 32° C.

18. The warmed saline travels back down the outer lumen of the cathetershaft and back to the chilled water bath where it is cooled to 1° C.

19. The pressure drops along the length of the circuit are estimated tobe 2-3 atmospheres.

20. The cooling can be adjusted by increasing or decreasing the flowrate of the saline. Monitoring of the temperature drop of the salinealong the heat transfer element will allow the flow to be adjusted tomaintain the desired cooling effect.

21. The catheter is left in place to provide cooling for 12 to 24 hours.

22. If desired, warm saline can be circulated to promote warming of thebrain at the end of the procedure.

The invention may also be used in combination with other techniques. Forexample, one technique employed to place working lumens or catheters indesired locations employs guide catheters, as mentioned above. Referringto FIG. 9, a guide catheter 102 is shown which may be advantageouslyemployed in the invention. A description below, in connection with FIG.22 et seq., describes an alternate embodiment of the invention employinga guidewire apparatus.

The guide catheter 102 has a soft tapered tip 104 and a retaining flange124 at a distal end 101. The soft tapered tip 104 allows an atraumaticentrance of the guide catheter 102 into an artery as well as a sealingfunction as is described in more detail below. The retaining flange 124may be a metallic member adhered to the guide catheter interior wall ormay be integral with the material of the tube. The retaining flange 124further has a sealing function described in more detail below.

The guide catheter 102 may have various shapes to facilitate placementinto particular arteries. In the case of the carotid artery, the guidecatheter 102 may have the shape of a hockey stick. The guide catheter102 may include a Pebax® tube with a Teflon® liner. The Teflon® linerprovides sufficient lubricity to allow minimum friction when componentsare pushed through the tube. A metal wire braid may also be employedbetween the Pebax® tube and the Teflon® liner to provide torqueabilityof the guide catheter 102.

A number of procedures may be performed with the guide catheter 102 inplace within an artery. For example, a stent may be disposed across astenotic lesion in the internal carotid artery. This procedure involvesplacing a guidewire through the guide catheter 102 and across thelesion. A balloon catheter loaded with a stent is then advanced alongthe guidewire. The stent is positioned across the lesion. The balloon isexpanded with contrast, and the stent is deployed intravascularly toopen up the stenotic lesion. The balloon catheter and the guidewire maythen be removed from the guide catheter.

A variety of treatments may pass through the guide catheter. Forexample, the guide catheter, or an appropriate lumen disposed within,may be employed to transfer contrast for diagnosis of bleeding orarterial blockage, such as for angiography. The same may further beemployed to deliver various drug therapies, e.g., to the brain. Suchtherapies may include delivery of thrombolytic drugs that lyse clotslodged in the arteries of the brain, as are further described in anapplication incorporated by reference above.

A proximal end 103 of the guide catheter 102 has a male luer connectorfor mating with a y-connector 118 attached to a supply tube 108. Thesupply tube 108 may include a braided Pebax® tube or a polyimide tube.The y-connector 118 connects to the guide catheter 102 via a male/femaleluer connector assembly 116. The y-connector 118 allows the supply tube108 to enter the assembly and to pass through the male/female luerconnector assembly 116 into the interior of the guide catheter 102. Thesupply tube 108 may be disposed with an outlet at its distal end. Theoutlet of the supply tube 108 may also be used to provide a workingfluid to the interior of a heat transfer element 110. The guide catheter102 may be employed as the return tube for the working fluid supply inthis aspect of the invention. In this embodiment, a heat transferelement 110 is delivered to the distal end 101 of the guide catheter 102as is shown in FIG. 10.

In FIG. 10, the heat transfer element 110 is shown, nearly in a workinglocation, in combination with the return tube/guide catheter 102. Inparticular, the heat transfer element 110 is shown near the distal end101 of the return tube/guide catheter (“RTGC”) 102. The heat transferelement 110 may be kept in place by a flange 106 on the heat transferelement 110 that abuts the retaining flange 124 on the RTGC 102. Flanges124 and 106 may also employ o-rings such as an o-ring 107 shown adjacentto the flange 106. Other such sealing mechanisms or designs may also beused. In this way, the working fluid is prevented from leaking into theblood.

The supply tube 108 may connect to the heat transfer element 110 (theconnection is not shown) and may be employed to push the heat transferelement 110 through the guide catheter 102. The supply tube should havesufficient rigidity to accomplish this function. In an alternativeembodiment, a guidewire may be employed having sufficient rigidity topush both the supply tube 108 and the heat transfer element 110 throughthe guide catheter 102. So that the supply tube 108 is preventing fromabutting its outlet against the interior of the heat transfer element110 and thereby stopping the flow of working fluid, a strut 112 may beemployed on a distal end of the supply tube 108. The strut 112 may havea window providing an alternative path for the flowing working fluid.

The heat transfer element 110 may employ any of the forms disclosedabove, as well as variations of those forms. For example, the heattransfer element 110 may employ alternating helical ridges separated byflexible joints, the ridges creating sufficient turbulence to enhanceheat transfer between a working fluid and blood in the artery.Alternatively, the heat transfer element 110 may be inflatable and mayhave sufficient surface area that the heat transfer due to conductionalone is sufficient to provide the requisite heat transfer. Details ofthe heat transfer element 110 are omitted in FIG. 10 for clarity.

FIG. 11 shows an alternate embodiment of the invention in which a heattransfer element 204 employs an internal supply catheter 216. The heattransfer element 204 is shown with turbulence-inducing invaginations 218located thereon. Similar invaginations may be located in the interior ofthe heat transfer element 204 but are not shown for clarity. Further, itshould be noted that the heat transfer element 204 is shown with merelyfour invaginations. Other embodiments may employ multiple elementsconnected by flexible joints as is disclosed above. A single heattransfer element is shown in FIG. 11 merely for clarity.

A return supply catheter 202 is shown coupled to the heat transferelement 204. The return supply catheter may be coupled to the heattransfer element 204 in known fashion, and may provide a convenientreturn path for working fluid as may be provided to the heat transferelement 204 to provide temperature control of a flow or volume of blood.

A delivery catheter 216 is also shown in FIG. 11. The delivery catheter216 may be coupled to a y-connector at its proximal end in the mannerdisclosed above. The delivery catheter 216 may be freely disposed withinthe interior of the return supply catheter 202 except where it isrestrained from further longitudinal movement (in one direction) by aretaining flange 210 disposed at the distal end 208 of the heat transferelement 204. The delivery catheter 216 may be made sufficiently flexibleto secure itself within retaining flange 210, at least for a shortduration. The delivery catheter 216 may have a delivery outlet 212 at adistal end to allow delivery of a drug or other such material fortherapeutic purposes. For example, a radio-opaque fluid may be dispensedfor angiography or a thrombolytic drug for thrombolysis applications.

For applications in which it is desired to provide drainage of theartery, e.g. laser ablation, the delivery catheter may be pulledupstream of the retaining flange 210, exposing an annular hole in fluidcommunication with the return supply catheter 202. The return supplycatheter 202 may then be used to drain the volume adjacent the retainingflange 210.

The assembly may also perform temperature control of blood in the arterywhere the same is located. Such temperature control procedures may beperformed, e.g., before or after procedures involving the deliverycatheter 216. Such a device for temperature control is shown in FIG. 12.In this figure, a working fluid catheter 222 is disposed within thereturn supply catheter 202 and the heat transfer element 204. In amanner similar to the delivery catheter 216, the working fluid cathetermay be freely disposed within the interior of the return supply catheter202 and may further be coupled to a y-connector at its proximal end inthe manner disclosed above. The working fluid catheter 222 may furtherbe made sufficiently flexible to secure itself within retaining flange210, at least for a short duration. The working fluid catheter 222 mayhave a plurality of outlets 214 to allow delivery of a working fluid.The outlets 214 are located near the distal end 224 of the working fluidcatheter 222 but somewhat upstream. In this way, the outlets 214 allowdispensation of a working fluid into the interior of the heat transferelement 204 rather than into the blood stream. The working fluidcatheter 222 may also be insulated to allow the working fluid tomaintain a desired temperature without undue heat losses to the walls ofthe working fluid catheter 222.

One way of using the same catheter as a delivery catheter and as aworking fluid catheter is shown in FIGS. 14 and 15. In FIG. 14, adelivery/working fluid catheter 248 is shown in a position similar tothe respective catheters of FIGS. 11 and 12. The delivery/working fluidcatheter 248 has working fluid outlets and a delivery outlet, and isfurther equipped with a balloon 244 disposed at the distal end. Balloon244 may be inflated with a separate lumen (not shown). By retracting thedelivery/working fluid catheter 248 to the position shown in FIG. 15,the balloon 244 may be made to seal the hole defined by retaining flange210, thereby creating a fluid-tight seal so that working fluid may bedispensed from outlets 246 to heat or cool the heat transfer element204.

One method of disposing a heat transfer device within a desired artery,such as the carotid artery, involves use of a guidewire. Referring toFIG. 13, a guidewire 232 is shown disposed within the interior of theheat transfer element 204. The heat transfer element 204 mayconveniently use the hole defined by retaining flange 210 to be threadedonto the guidewire 232. A separate embodiment of the invention, alsoemploying a guidewire, is described below in connection with FIG. 22 etseq.

Numerous other therapies may then employ the return supply catheter andheat transfer element as a “guide catheter”. For example, various laserand ultrasound ablation catheters may be disposed within. In this way,these therapeutic techniques may be employed at nearly the same time astherapeutic temperature control, including, e.g., neuroprotectivecooling.

The use of an additional lumen was disclosed above in connection withpassing a variety of treatments through the guide catheter. For example,an additional lumen may be employed to transfer contrast for diagnosisof bleeding or arterial blockage, such as for angiography. Such anadditional lumen may be defined by a drug delivery catheter which formsan integral or at least integrated part of the overall inventivecatheter assembly. The same may be employed to deliver various drugtherapies, e.g., to the brain. The use of an additional lumen wasfurther mentioned in connection with expansion of a balloon that may beused to occlude a drug delivery lumen outlet.

FIG. 16 depicts an implementation of an embodiment of the inventionemploying just such a third lumen. In FIG. 16, a third lumen 316 is asmall central lumen defined by a drug delivery catheter substantiallycoaxial with the supply and return catheters. A return catheter 302defining an outlet lumen 320 is coupled to a heat transfer element 304as before. The heat transfer element 304 may have turbulence-inducinginvaginations 306 thereon. Within the heat transfer element 304 and thereturn catheter 302 is an inlet lumen 318 defined by a supply catheter310. The inlet lumen 318 may be used to deliver a working fluid to theinterior of the heat transfer element 304. The outlet lumen 320 may beused to return or exhaust the working fluid from the heat transferelement 304. As above, their respective functions may also be reversed.The radius of the return catheter may be greater or less than the radiusof the supply catheter. The working fluid may be used to heat or coolthe heat transfer element which in turn heats or cools the fluidsurrounding the heat transfer element.

A drug delivery catheter 312 defines the third lumen 316 and as shownmay be coaxial with the inlet lumen 318 and the outlet lumen 320. Ofcourse, the delivery catheter 312 may be also be off-axis or non-coaxialwith respect to the inlet lumen 318 and the outlet lumen 320.

For example, as shown in FIG. 17, the drug delivery catheter may be alumen 316′ within the return catheter and may be further defined by acatheter wall 312′. As another example, as shown in FIG. 18, the drugdelivery catheter may be a lumen 316″ adjacent to and parallel to thereturn catheter and may be further defined by a catheter wall 312″. Inan alternative embodiment, more than one lumen may be provided withinthe return catheter to allow delivery of several types of products,e.g., thrombolytics, saline solutions, etc. Of course, the supplycatheter may also be used to define the drug delivery catheter. The drugdelivery catheter may be substantial coaxial with respect to the returncatheter or supply catheter or both, or may alternatively be off-axis.The drug delivery catheter includes an outlet at a distal end thereof.The outlet may be distal or proximal of the distal end of the return orsupply catheters. The outlet may be directed parallel to the return orsupply catheters or may alternatively be directed transverse of thereturn or supply catheters.

The device may be inserted in a selected feeding vessel in the vascularsystem of a patient. For example, the device may be inserted in anartery which feeds a downstream organ or which feeds an artery which, inturn, feeds a downstream organ. In any of the embodiments of FIGS.16-18, the drug delivery catheter lumen may be used to deliver a drug,liquid, or other material to the approximate location of the heattransfer element. Such delivery may occur before, after, orcontemporaneous with heat transfer to or from the blood. In this way,drugs or enzymes which operate at temperatures other than normal bodytemperature may be used by first altering the local blood temperaturewith the heat transfer element and then delivering the temperaturespecific drug, such as a temperature specific thrombolytic, which thenoperates at the altered temperature. Alternatively, such “third” lumens(with the supply and return catheters for the working fluid defining“first” and “second” lumens) may be used to remove particles, debris, orother desired products from the blood stream.

FIGS. 19 and 20 show another embodiment of the invention that is relatedto the embodiment of FIG. 17. In this embodiment, several additionalsealed lumens are disposed in the return catheter. Some of the lumensmay be for drug delivery and others may be used to enhance turbulence ina manner described below. The sealed lumens are in pressurecommunication with a supply of air to inflate the same. In FIG. 19, areturn catheter 302′ has one lumen 316′″C as shown for drug delivery.Another, lumen 316′″I, is shown which may be employed to alter thegeometry and shape of the overall catheter. That is, inflating lumen316′″I causes the lumen to expand in the same way that inflating aballoon causes it to expand. In order to allow for the expansion,appropriately reduced return catheter wall thicknesses may be employed.Also, inflatable lumens 316′″A-B and 316′″D-N may be distributed in asubstantially symmetric fashion around the circumference of the catheterfor a uniform inflation if desired. Of course, less distortion underinflation may occur at or adjacent lumens such as 316′″C used for drugdelivery, as these do not inflate.

The inflatable lumens 316′″A-B and 316′″D-N may be caused to inflateunder influence of, e.g., an air compressor with a variable air deliveryflow. Rapid pulses of air may be used to inflate the lumens 316′″A-B and316′″D-N in a rapid and repeated fashion. By so doing, the outer wallsdefining these lumens move rapidly into and out of the bloodstreamaround the catheter, inducing turbulence. Preferably, the amplitude ofthe vibrations is large enough to move the outer walls defining thelumens out of the boundary layer and into the free stream of blood. Thiseffect produces turbulence which is used to enhance heat transfer. As itis important to induce turbulence only near the heat transfer element,the area of appropriate wall thickness to allow for inflation need onlybe at, near, or adjacent the portion of the return catheter exteriorwall adjacent the heat transfer element. In other words, the returncatheter wall only requires reduction near the heat transfer element.The remainder of the catheter wall may remain thick for strength anddurability.

The supply catheter 310 may be constructed such that the same does notcontact the interior of the distal end 308 of the heat transfer element,which may cause a subsequent stoppage of flow of the working fluid. Suchconstruction may be via struts located in the return catheter 302 thatextend radially inwards and secure the supply catheter 310 fromlongitudinal translations. Alternatively, struts may extendlongitudinally from the distal end of the supply catheter 310 and holdthe same from contacting the heat transfer element. This construction issimilar to strut 112 shown in FIG. 10.

FIG. 21 shows an alternate method of accomplishing this goal. In FIG.21, a heat transfer element 304′ has an orifice 326 at a distal end 308.A supply catheter 310′ is equipped with a drug delivery catheter 312′extending coaxially therein. The drug delivery catheter 312 may beformed of a solid material integral with supply catheter 310′, or thetwo may be bonded after being constructed of separate pieces, or the twomay remain separate during use, with a friction fit maintaining theirpositions with respect to each other. The supply catheter 310′ is “inposition” when a tapered portion 324 of the same is lodged in the hole326 in the heat transfer element 304′. The tapered portion 324 should belodged tightly enough to cause a strong friction fit so that workingfluid does not leak through the hole 326. However, the tapered portion324 should be lodged loosely enough to allow the supply catheter 310′ tobe removed from the heat transfer element 304′ if continued independentuse of the return catheter is desired.

The supply catheter 310′ has a plurality of outlets 322. Outlets 322 areprovided at points generally near or adjacent the distal end of thesupply catheter 310′. The outlets are provided such that, when thesupply catheter 310′ is in position, the outlets generally face the heattransfer element 304′. In this way, the working fluid, emerging from theoutlets 322, more directly impinges on the interior wall of the heattransfer element 304′. In particular, the working fluid exits theinterior of the supply catheter and flows into a volume defined by theexterior of the supply catheter and the interior of the heat transferelement.

For clarity, FIG. 21 does not show the invaginations on the interiorwall of the heat transfer element 304′. However, it will be understoodthat such invaginations may be present and may allow for enhanced heattransfer in combination with the emerging working fluid.

In the embodiments of FIGS. 9, 11, and 13-21, various types of catheterassemblies employing drug delivery catheters are described. In thoseembodiments, and particularly in the embodiments such as FIGS. 11, 14-16and 21, in which a distal end of the drug delivery catheter protrudessubstantially from the distal end of the remainder of the catheterassembly, a therapy may be performed in which the distal end of thecatheter is embedded into a clot to be dissolved. An enzyme solution,such as a warm or cool enzyme solution, may then be sent directly intothe clot to locally enhance the fibrinolytic activity.

In particular, the catheter may be placed as described above. In thisprocedure, however, the catheter is placed such that the tip of theprotruding drug delivery catheter touches, is substantially near, orbecomes embedded within the clot. An enzyme solution or other such drugis then delivered down the drug delivery catheter directly into the clotor into the volume of blood surrounding the clot. The enzyme solutionmay include tPA, streptokinase, urokinase, pro-urokinase, combinationsthereof, and may be heated to enhance fibrinolytic activity. In arelated embodiment, the solution may be a simple heated saline solution.The heated saline solution warms the clot, or the volume surrounding theclot, again leading to enhanced fibrinolytic activity.

In these procedures, it is advantageous to use embodiments of theinvention in which the distal tip of the drug delivery catheter issubstantially protruding, or is distal, from the remainder of thecatheter assembly. In this way, the distal tip may be disposed adjacentto or within a clot without being obstructed by the remainder of thecatheter assembly.

As mentioned above, the catheter and heat transfer element may beconveniently disposed in a predetermined position using a guidecatheter. The predetermined position may be one in which blood flowspast the heat transfer element towards an organ to be cooled. FIG. 13shows one such embodiment in which a guidewire passes down the center ofthe heat transfer element.

FIG. 22 shows a related embodiment of a cooling device including aguidewire apparatus. Referring to FIG. 22, a cooling device includes acatheter 400 and a heat transfer element 401, both shown incross-section. The catheter 400 is coupled to the heat transfer element401 via a mount 410. Mount 410 may be an adhesive material, afriction-fit, a snap-fit, or other such techniques or devices as areknown in the art, etc. At least two lumens run the length of thecatheter 400 and heat transfer element 401: an inlet lumen 402 definedby an inlet tube 405 and an outlet lumen 407 defined by an outlet orreturn tube 404. A guidewire lumen 403 is defined by guidewire lumen406. Guidewire lumen 406 may be employed to maneuver the cooling devicealong a guidewire 408. It is noted here that guidewire 408 may itself bea microcatheter useful for delivering drugs or other such therapies.

The heat transfer element 401 is also shown schematically in FIG. 22.Various details have been omitted for clarity. In the figure, the heattransfer element 401 is formed from successive segments. Alternatinghelices, forming invaginations, are shown by elements 412, 412′, 412″,and 412′″. The elements shown in FIG. 22 are not perfect helices, butare intended to demonstrate how such elements may be configured in thesystem. As can be seen, the helicity may alternate between successiveadjacent segments to enhance turbulence and thus heat transfer.

Adjacent segments may be coupled by thin tubes of metal or polymericmaterials, or alternatively by metal bellows. Elements 414, 414′, 414″are schematic in nature and are intended to demonstrate the location ofsuch coupling segments.

An optional feature which may be employed is a spring-tip 434. Thespring-tip 434 is a tightly wound spring of small radius which allowsthe cooling device to navigate tortuous vasculature easily and withoutdamage to vessel walls.

At various locations, an eyelet or equivalent structure may be providedthrough which a guidewire may pass. The eyelet or equivalent structuresneed not be employed on the catheter 400, as the guidewire lumen 403serves this purpose. However, the eyelet or equivalent structures may beespecially advantageously provided on the heat transfer element and/oron the spring-tip 434. A break-out of the eyelet structure is shown inFIG. 22. In the break-out drawing, a portion of a bellows 414 is shownsupporting an eyelet mount 422. Mount 422 may then support eyelet 424through which guidewire 408 passes. Of course, an eyelet 424 is not theonly type of structure which may be employed: fork-type structures orother similar guiding structures may also be employed. Similarconsiderations hold for the eyelet structures 422′/424′, 422″/424″, and438/436 (the latter at the end of the spring-tip 434).

In use, the guidewire 408 is placed into the vasculature of a patient.For an application of brain cooling, the guidewire may be run from thefemoral artery through the vasculature into the internal carotid artery.The heat transfer element 401 may then be threaded onto the guidewire408 by first threading eyelet 438 onto the guidewire 408. One or more ofeyelets 424″, 424′, and 424 may then be threaded onto the guidewire 408successively. Finally, the guidewire 408 may be run through theguidewire lumen 403 (defined by guidewire tube 406). The cooling device,defined by catheter 400 and heat transfer element 401, may then beinserted into the patient's vasculature along the path defined by theguidewire 408. The applications of the cooling device, which mayalternatively provide heating rather than cooling, are discussed above.

The tip of the guidewire 408 may contain or be part of a temperaturemonitor. The temperature monitor may be employed to measure thetemperature upstream or downstream of the heat transfer element andcatheter, depending on the direction of blood flow relative to thetemperature monitor. The temperature monitor may be, e.g. a thermocoupleor thermistor.

An embodiment of the invention employing a thermocouple is shown in FIG.23. In this figure, a thermocouple 440 is mounted on the end of theguidewire 408. For the temperatures considered in blood heating orcooling, most of the major thermocouple types may be used, includingTypes T, E, J, K, G, C, D, R, S, B.

In an alternative embodiment, a thermistor may be used as shown in FIG.24. The figure shows a thermistor device 441 attached to the end of theguidewire 408. Thermistors are thermally-sensitive resistors whoseresistance changes with a change in body temperature. The use ofthermistors may be particularly advantageous for use intemperature-monitoring of blood flow past cooling devices because oftheir sensitivity. For temperature monitoring of body fluids,thermistors that are mostly commonly used include those with a largenegative temperature coefficient of resistance (“NTC”). These shouldideally have a working temperature range inclusive of 25° C. to 40° C.Potential thermistors that may be employed include those with activeelements of polymers or ceramics. Ceramic thermistors may be mostpreferable as these may have the most reproducible temperaturemeasurements. Most thermistors of appropriate sizes are encapsulated inprotective materials such as glass. The size of the thermistor, forconvenient mounting to the guidewire and for convenient insertion in apatient's vasculature, may be about or less than 15 mils. Largerthermistors may be used where desired. Of course, various othertemperature-monitoring devices may also be used as dictated by the size,geometry, and temperature resolution desired.

A signal from the temperature monitoring device may be fed back to thesource of working fluid to control the temperature of the working fluidemerging therefrom. Referring to FIG. 25, such a feedback signal 458 isshown. In particular, FIG. 25 shows schematically the catheter connectedto a source of working fluid 452. As is obvious, the aspect ratio of thecatheter shown is highly atypical and is shown in this fashion solelyfor clarity. The figure shows that a proximal end of supply lumen 402defined by supply tube 405 is connected at an output port 454 to thesource of working fluid 452. The return lumen 407 defined by the tube404 is similarly connected at an input port 460 to the source of workingfluid 452. The source of working fluid 452 can control the temperatureof the working fluid emerging from the output port 454. A signal from acircuit 458 may be inputted to the source of working fluid 452 at aninput 456. The signal from circuit 458 may be from the thermocouple 440,or may alternatively be from any other type of temperature-monitoringdevice, such as at the tip of the guidewire 408.

The signal may advantageously be employed to alter the temperature, ifnecessary, of the working fluid from the source 452. For example, if thetemperature-monitoring device senses that the temperature of the bloodflowing in the feeding vessel of the patient's vasculature is belowoptimal, a signal may be sent to the source of working fluid 452 toincrease the temperature of the working fluid emerging therefrom. Theopposite may be performed if the temperature-monitoring device sensesthat the temperature of the blood flowing in the feeding vessel of thepatient's vasculature is above optimal.

The invention has been described with respect to certain embodiments. Itwill be clear to one of skill in the art that variations of theembodiments may be employed in the method of the invention. Accordingly,the invention is limited only by the scope of the appended claims.

What is claimed is:
 1. A guidable catheter for heating or cooling asurrounding fluid in a vessel in the vasculature of a patientcomprising: a heat transfer element, the heat transfer element having atleast one exterior surface irregularity shaped and arranged to createmixing in a surrounding fluid in a vessel, wherein the heat transferelement has coupled thereto at least one eyelet configured to receivethe guidewire threaded therethrough; a supply catheter having a portiondisposed within the heat transfer element to deliver a working fluid toan interior of the heat transfer element; a return catheter to return aworking fluid from the interior of the heat transfer element; and aguidewire tube adjacent one of the supply catheter or the returncatheter and running substantially parallel to the axis of the guidablecatheter to receive a guidewire, wherein the heat transfer element isformed from at least two heat transfer segments, adjacent heat transfersegments joined by bellows, and wherein the eyelets are attached to theheat transfer element at the bellows.
 2. The device of claim 1, wherein:the surface irregularity includes a helical ridge and a helical grooveformed on each of successive heat transfer segments; and the helicalridge on each heat transfer segment has an opposite helical twist to thehelical ridges on adjacent heat transfer segments.
 3. A guidablecatheter for heating or cooling a surrounding fluid in a vessel in thevasculature of a patient, comprising: a heat transfer element, the heattransfer element having at least one exterior surface irregularityshaped and arranged to create mixing in a surrounding fluid in a vessel,wherein the heat transfer element has coupled thereto at least oneeyelet configured to receive the guidewire threaded therethrough; asupply catheter having a portion disposed within the heat transferelement to deliver a working fluid to an interior of the heat transferelement; a return catheter to return a working fluid from the interiorof the heat transfer element; and a guidewire tube adjacent one of thesupply catheter or the return catheter and running substantiallyparallel to the axis of the guidable catheter to receive a guidewirewherein the heat transfer element is formed from at least two heattransfer segments, adjacent heat transfer segments joined by a thintube, and wherein the eyelets are attached to the heat transfer elementat the thin tube.
 4. The device of claim 1, wherein the thin tube isformed of a metal.
 5. The device of claim 1, wherein the thin tube isformed of a polymer material.